MITOCHONDRIAL DISEASE PRIORITY SETTING PARTNERSHIP: Setting research priorities with patients, carers and clinicians.
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MITOCHONDRIAL DISEASE
PRIORITY SETTING
PARTNERSHIP:
Setting research priorities with
patients, carers and clinicians.
Page 1
ABOUT THE COLLABORATORS
The Lily Foundation is the UK’s leading mitochondrial disease charity. Our
mission is to improve the lives of people affected by mitochondrial diseases. We
are working towards a future where mitochondrial diseases can be effectively
treated or cured.
LHON Society is a patient-led support group for a rare condition called Leber’s
Hereditary Optic Neuropathy (LHON). Our group is comprised of LHON patients
and family members. We aim to provide support and information, facilitate
research, provide guidance and representation, and promote up to date
knowledge and understanding of LHON.
Metabolic Support UK (formerly known as Climb) are the leading patient
organisation for Inherited Metabolic Disorders supporting thousands of patients
worldwide.
Muscular Dystrophy UK are the UK charity for individuals and families living
with muscle-wasting conditions. We support research to drive the development
of effective treatments and cures. We ensure access to specialist NHS care and
support. We provide services and promote opportunities to enable individuals
and their families to live as independently as possible.
The James Lind Alliance (JLA) is a non-profit making initiative established
in 2004. It brings patients, carers and clinicians together in a Priority Setting
Partnership (PSPs) to identify and prioritise the Top 10 unanswered questions
that they agree are the most important. The aim is to make sure that health
research funders are aware of the issues that matter most to the people who
need to use the research in their everyday lives.
We are the national charity working to improve the lives of patients and families
affected by genetic, rare and undiagnosed conditions. We are an alliance of over
200 patient organisations.
Healthcare professionals from the following institutions collaborated in this
work:
―― Highly Specialised Service for Rare Mitochondrial Disease, Newcastle,
Oxford and London
―― The University Hospital of Wales, Cardiff
―― National Hospital for Neurology and Neurosurgery, London
―― UCL Great Ormond Street Institute of Child Health
―― Hinchingbrooke and Addenbrooke’s Hospitals
The project was funded by a Public Engagement grant from Wellcome.
Published by: Published by: Genetic Alliance UK, on behalf of the Mitochondrial Disease
Priority Setting Partnership steering group
Telephone: +44 (0) 20 7831 0883
Email: amy.hunter@geneticalliance.org.uk
Website: geneticalliance.org.uk
Published: February 2020
Genetic Alliance UK registered charity numbers: 1114195 & SC039299. Registered company number: 05772999
Page 1
CONTENTS
3 Why set priorities for research into rare mitochondrial
disease?
4 Top 10 pirorities for research into rare mitochondrial
disease
5 Setting the limits of this priority setting exercise
7 How were the priorities identified?
9 The priority setting workshop
10 Next steps
11 Acknowledgments
12 Appendix: The shortlist of research questions
Page 2
WHY SET PRIORITIES FOR RESEARCH INTO RARE MITOCHONDRIAL DISEASE? Despite growing research activity in the UK and across the globe, there are still many unanswered questions about mitochondrial disease. Resources for research are limited and consequently it is important for researchers and funding organisations to understand which are the most important questions for research to address from the point of view of patients, carers and healthcare professionals, so that research funding can be targeted accordingly. As for many rare diseases, mitochondrial disease has received less research attention than common conditions, so the need to consult with those affected is intensified. The diversity in how mitochondrial disease affects individuals is a further challenge to attracting research. Rarity also means that it can be hard to reach a critical mass in consultations such as this, but by bringing together a motivated team of patient groups and healthcare professionals covering a range of related conditions, we are pleased to have secured the input of over 250 individuals to the process. This Priority Setting Partnership aimed to stimulate research by finding out what people with these conditions, their carers and healthcare professionals believe to be the most important questions about the care, treatment, management and the natural history of mitochondrial disease, for adults and children. “Given the diverse nature of mitochondrial disease it is often easy to forget that we are part of the same “family.” This exercise has been a revelation in showing how much we can benefit from a common approach and a renewed focus on what is really important for patients.” Steering Group member. “Mitochondrial disorders have multiple causes, can affect people of all ages, and all body systems can be involved. It is therefore remarkable to bring patients and clinicians together to create a shared list of research priorities to set the agenda for research that matters for our community.” Steering Group member. Page 3
THE TOP 10 PRIORITIES
FOR RESEARCH INTO
MITOCHONDRIAL DISEASE
1. Could an understanding of the cellular and molecular processes in
mitochondrial disease lead to new treatments?
2. Can the damage to cells caused by mitochondrial disease be repaired
(e.g. to restore hearing, vision, or repair the pancreas)?
3. What are the biological mechanisms that cause mitochondrial disease to
get worse over time?
4. What biomarkers (biological markers that can be measured e.g. in blood
samples) could be used to diagnose mitochondrial disease and to track
its progress?
5. Could gene therapy help people with mitochondrial disease?
6. What are the psychological impacts of mitochondrial disease? What
are the best ways to provide psychological support for people with
mitochondrial disease and their families?
7. What are the best ways to reduce the risk of stroke-like episodes in people
with mitochondrial disease?
8. What factors could trigger the start of mitochondrial disease in people
who have a genetic mutation?
9. Why are people with the same genetic mutation affected so differently in
mitochondrial disease?
10. What are the most effective ways to treat and manage fatigue?
Page 4
SETTING THE LIMITS OF THIS
PRIORITY SETTING EXERCISE
The aim of the PSP was to identify the unanswered Diversity and inclusion
questions about care, treatment, management
and the natural history of mitochondrial disease,
for adults and children, from patient and clinical Ethnic diversity
perspectives. The questions that patients and The Breaking Down Barriers project awarded
clinicians agree are the most important are funding to the PSP to support activities aimed at
then prioritised. Primary mitochondrial disease, broadening the ethnic diversity of participants. We
in which the function of the mitochondria is created a series of videos for use with social media
affected by a nuclear or mitochondrial genetic in four languages to encourage people whose first
mutation, was the project’s core focus. Secondary language is not English to take part in the second
mitochondrial conditions were excluded because survey and the workshop. Mitochondrial disease
they accompany many non-mitochondrial diseases does not appear to affect certain populations
so would extend the scope too far. Research to more than others, so our choice of languages
improve diagnosis was not included in the scope was a pragmatic decision based on the patient
of the project because this risked broadening the populations known to the clinics involved, and
scope too much, and because there is already a on the availability of speakers during what was a
strong focus on this area in rare disease policy short timeline. Videos were produced in Welsh,
development. Farsi, Arabic and Malay, and were distributed
widely including through Facebook using their
The PSP steering group actively took the facility to target specific populations. Too few
decision to include both adults and children respondents declared their ethnicity in either
in a single prioritisation process because the survey to confidently assess whether the second
questions collected during the first phase were survey respondents were more diverse. Of those
generally not focussed on just one or the other. who did declare, 4% said they have a black and
minority ethnic background in the first survey,
and 5% in the second (less than the UK population
in general). However a greater proportion of
workshop attendees had a background other than
white British.
More targeted, face-to-face engagement may
have helped boost ethnic diversity in the survey
respondents, but this would have taken more time
and resource than the project had available. It is
notable that the mitochondrial patient groups
involved report challenges in engaging with BAME
families, indicating that careful assessment of the
underlying reasons would be required to create a
successful plan for improving diversity in future
projects.
Page 5
Inclusion
Mitochondrial disease can lead to a range of disabilities such as vision loss, hearing loss, and mobility
and coordination problems. The way that mitochondrial disease affects an individual can be influenced
by their specific genetic change and can vary hugely from person to person. We took several steps to
support inclusion for people with a range of disabilities:
―― The online surveys were published in large font, and piloted by vision-impaired individuals to ensure
readability with screen-reading software across a variety of platforms.
―― The surveys were also offered on paper and as PDF attachments for access with screen readers.
―― Workshop attendees were asked to advise on their specific access needs, which were then met e.g.
meeting an attendee with a visual impairment at the train station, ensuring a T-loop for hearing
aids was available, arranging rooms to allow for wheelchair access, and ensuring that all rooms and
accessible toilets were on the same floor.
―― The materials used in the workshop were printed with large font, and the needs of participants were
flagged to the facilitators, who were able to support individuals e.g. through reading the question
cards often and describing carefully changes being made to the order of prioritisation.
Page 6
HOW WERE THE
PRIORITIES IDENTIFIED?
Getting started by many people, in slightly different ways.
The project was driven by a steering group of Similar questions were grouped together and
patient organisation representatives and clinicians. an overarching question was written which
The partnership was officially launched in summer summarised all the questions in the group. A small
2018. number of questions were only asked once. These
were added to the list of overarching questions.
We then checked the published evidence from
The first survey research that has been carried out in the past and
People with a primary mitochondrial disease, their
concluded that previous research has not fully
family members and the healthcare professionals
answered any of the remaining questions and so
who support them, were asked to identify the
no further questions were removed at this stage. At
questions they would like answered by research.
this point, we had 42 unanswered questions – this
They submitted their questions via an online
was our ‘longlist’ (available on request).
survey in March and April 2019. A paper version of
the survey was also made available via a PDF that
could be printed locally for distribution.
The steering group members and organisations
supporting the project sent the survey out to their
networks, via email, newsletters, social media and
websites. A total of 147 people submitted a total
of 709 questions. The people who responded were
people with a mitochondrial disease (34%), carers
or relatives (32%), and healthcare professionals
(34%). The majority (64%) were female.
Processing the survey results
Among the 709 questions submitted through
the first survey were some that were asking for
information or advice, that is, questions that do
not need research to be answered (85). A further
53 were outside the scope of the project or asking
about access to services. Questions about access
might need to be addressed through changing
policy and practice rather than research. All of
these questions were removed.
Of the remaining questions, some were asked
Page 7
The second survey
In the second survey we asked people to rank each of the 42 questions in the longlist to indicate the
degree of its importance to them. The second survey went out to the same networks as the first survey
in order to gather as much input as possible, with additional promotion through four videos in different
languages. The survey was live in October and November 2019 resulting in 166 responses: 63% were
patients, 21% were carers or relatives, and 16% were healthcare professionals. A majority of respondents
were female (66%).
The questions in the second survey were presented in random order and were randomised each time
an individual accessed the survey. Participants were asked to consider each of the 42 questions, choose
10 and then rank them in order of priority (1 being top priority). Equal weighting was given to responses
from patients, carers and healthcare professionals.
This exercise resulted in all the questions being given a score and placed in order separately for each type
of respondent. The lists were then combined, resulting in a final list of shared priorities, from 1 to 42. The
top 24 questions – the ‘shortlist’ – were taken to the next step of the process.
Page 8
THE PRIORITY SETTING WORKSHOP The 24 shortlisted questions were discussed at a workshop held in London in January 2020. Invitations to the workshop were sent out through the steering group: 32 people participated, comprising 8 people with a mitochondrial disease, whose conditions affected vision, control of movement and epilepsy; 9 carers/family members; 2 patient organisation representatives; 13 healthcare professionals from 9 different disciplines. Given the complex health needs of many individuals with mitochondrial disease, it was important to include a wide range of professionals. Of the 32 participants, 7 were members of the steering group. The participants were asked to look at the 24 shortlisted questions before they came and to think about how they would rank them in order of importance. By attending the workshop, and taking part in a number of small group discussions, “Really wonderful to meet so many people everyone was able to hear one another’s views on who are involved in managing, researching and which questions were most and least important supporting mitochondrial disease. Hearing from and why. This helped the group as a whole to reach patients and families has been enlightening and an agreement about which questions should be a raised awareness of the challenges they face.” priority. Workshop attendee. The top 10 questions are listed in full on page 4 of this report. The full list of 24 questions in order “Excellent [workshop]. Real privilege to be part of importance as agreed by the people at the of the process.” workshop is given in the appendix. Workshop attendee. Page 9
NEXT STEPS
The JLA Mitochondrial Disease Priority Setting their applications for funding. If a researcher
Partnership, by identifying these priority questions receives funding to address any of the listed
for research, seeks to ensure that future research priorities, we ask that they please inform the
is focused on the issues that matter most to JLA.
people with mitochondrial disease, their carers
and relatives and the healthcare professionals ―― We encourage funders, researchers and all
who support them. The steering group will interested parties to share this report with
disseminate the questions through their patient others and to raise awareness of the need for
and professional networks, by presentation at more research on mitochondrial disease in the
academic and patient conferences, publication in a UK.
peer-reviewed journal, and by liaising directly with
research funders. If you have any queries or comments about this
work, please contact Amy Hunter: amy.hunter@
“The energy and passion in the room at the geneticalliance.org.uk.
final prioritisation meeting was palpable and
this highlighted in a very real and personal way Further information about the project can be found
just how important these questions are to the at: jla.nihr.ac.uk/priority-setting-partnerships/
patients and their families and carers” mitochondrial-disease.
Steering Group member.
If you would like more information and advice
A call to arms about mitochondrial disease or LHON, please
Many people gave their time and effort to submit contact:
their questions and to work through the JLA
process to identify the final top 10 questions for ―― The Lily Foundation thelilyfoundation.org.uk
future research. We want to ensure that these
―― LHON Society lhonsociety.org
efforts are respected and recognised and therefore:
―― Further information can also be found at
―― We encourage research funders to include mitochondrialdisease.nhs.uk
these priorities in their research strategy and to
target these topics for future research funding.
―― We encourage researchers to focus their efforts
on answering the highest priority questions
and to mention the JLA Mitochondrial PSP in
Page 10ACKNOWLEDGEMENTS Thanks to our partners who supported this project, the Steering Group members, the James Lind Alliance advisers and support staff who advised and facilitated the partnership and the people who took part at all the different stages. Thanks to Kristina Staley who analysed the responses to the first survey, and to Amy Simpson who analysed the responses to the second survey and who supported the workshop on the day. This project was funded by Wellcome. Members of the Steering Group were: Lyndsey Butterworth, Science Communication, Lily Foundation Catherine Feeney, Mitochondrial Nurse Consultant, Newcastle Hospitals NHS Foundation Trust Tracey Graves, Consultant Neurologist, Hinchingbrooke and Addenbrooke’s Hospitals, and The National Hospital for Neurology and Neurosurgery Sarah Holmes, Clinical Specialist Physiotherapist Neuro-Muscular Diseases, UCLH Centre for Neuromuscular Diseases, The National Hospital of Neurology and Neurosurgery Pushpa Hossain, Patient Access to Diagnosis & Treatment Researcher, Metabolic Support UK Amy Hunter, Director of Research, Genetic Alliance UK Jo Lowndes, Genetic Counsellor, Oxford University Hospitals NHS Foundation Trust Shamima Rahman, Consultant Metabolic Paediatrician, UCL Great Ormond Street Institute of Child Health Jenny Sharpe, Research Communications Manager, Muscular Dystrophy UK Rhys Thomas, Honorary Consultant in Epilepsy, NHS Highly Specialised Service for Rare Mitochondrial Diseases, Newcastle upon Tyne & Intermediate Clinical Lecturer, Translational and Clinical Research Institute, Newcastle University Sheela Upadhyaya, JLA Advisor, independent Professor Marcela Votruba, Honorary Consultant Ophthalmologist and Professor of Ophthalmology, University Hospital Wales, Cardiff Russell Wheeler, Patient Advocate & Trustee, Leber’s Hereditary Optic Neuropathy Society James Lind Alliance Adviser and Chair of the Steering Group: Sheela Upadhyaya, JLA “At the Lily Foundation, our mission is the improve the lives of people with mitochondrial disease. We believe that identifying the top ten research priorities for mitochondrial disease will ensure that future research can help us achieve our ultimate goal and we are very proud to have been involved in the PSP process.” Steering Group member Page 11
APPENDIX: THE SHORTLIST
OF RESEARCH QUESTIONS
1. Could an understanding of the cellular and molecular processes in mitochondrial disease lead to
new treatments?
2. Can the damage to cells caused by mitochondrial disease be repaired (e.g. to restore hearing,
vision, or repair the pancreas)?
3. What are the biological mechanisms that cause mitochondrial disease to get worse over time?
4. What biomarkers (biological markers that can be measured e.g. in blood samples) could be used
to diagnose mitochondrial disease and to track its progress?
5. Could gene therapy help people with mitochondrial disease?
6. What are the psychological impacts of mitochondrial disease? What are the best ways to provide
psychological support for people with mitochondrial disease and their families?
7. What are the best ways to reduce the risk of stroke-like episodes in people with mitochondrial
disease?
8. What factors could trigger the start of mitochondrial disease in people who have a genetic
mutation?
9. Why are people with the same genetic mutation affected so differently in mitochondrial disease?
10. What are the most effective ways to treat and manage fatigue?
11. What are the genetic mutations that cause mitochondrial disease and how do they cause it?
12. Could a specific diet and/or supplements benefit people with mitochondrial disease?
13. What can prevent mitochondrial disease from getting worse over time?
14. How do the different genetic mutations cause the symptoms people experience with
mitochondrial disease?
15. Is there a way to predict who will become ill with mitochondrial disease, and whose symptoms
will be worse?
16. What can prevent the start of mitochondrial disease in people with a genetic mutation?
17. What are the most effective ways to treat and manage problems with muscle weakness?
18. What aspects of their health should be monitored over time and how often in people with
mitochondrial disease?
19. What are the most effective ways to treat and manage problems with memory, concentrating,
learning and making decisions?
Page 1220. What are the most effective ways to treat and manage pain?
21. What are the most effective ways to treat and manage problems with balance and co-ordination?
22. How does mitochondrial disease change over time as people get older?
23. Does exercise benefit people with mitochondrial disease? If yes, what is the best form of exercise?
24. What causes the genetic mutation in people with mitochondrial disease whose parents don’t have
the mutation?
Page 13Page 14
The PSP and its findings are endorsed by the
following European Reference Networks:
EpiCARE, ERN-EYE, Euro-NMD and MetabERN.
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